Figure 4
From: Electric field modulation of ERK dynamics shows dependency on waveform and timing
Time characteristics of EF-induced inhibition and comparison with EGFR inhibitor. (A–D) Periodic modulation of ERK inhibition induced by short EF stimuli. Representative time traces of ERKTR ratio of individual cells (n = 123) when multiple cycles of 1 min EF stimuli are applied to the same group of cells with different time intervals, thicker lines are population average, shadow region shows 25th and 75th percentile values. Interval time: (A) 30 min, (B) 20 min, (C) 10 min, (D) 5 min. (E) Comparison of ERK inhibition peak amplitude from the averaged ERKTR ratios (red traces as shown in A–D) when different interval times were used between EF stimulations. (F) Fluctuation of ERK with inhibitions when long sub-threshold 50 kHz square wave EF stimulation was applied. Dash lines mark the beginning (at 11 min) and the end (at 80 min) of the EF stimulation. The light blue traces are representative raw ERKTR ratio from individual cells. The bold red trace is the averaged ERKTR ratio from all cells (n = 20). The light red shadow gives the standard deviation. (G) Comparison of ERK inhibition induced by EGFR inhibitor and EF. Red trace: ERKTR ratio showing ERK inhibition induced when 1 µM EGFR inhibitor afatinib was applied (marked by the black arrow). Green trace: ERKTR ratio showing inhibitive ERK response as two separate 3 min long EF stimulations (marked by the green half arrows) were applied after the application of afatinib (marked by the black arrow). EF independently demonstrated a quicker and more profound inhibition of ERK on top of the slower chemical inhibition process, suggesting EGFR may not be the only component impacted by EF.
